One of the reasons why viral infections can be difficult to treat is the high mutation rate displayed by many viruses, which can sometimes allow them to evade our immune systems and develop resistance to drugs. In this article, Shivani looks into the evidence gathered by scientists around the world on mutations in the genome of SARS-CoV‑2, the virus that causes COVID-19.
In December 2019, several people in China were diagnosed with a new respiratory disease caused by an unknown virus. Following this, more cases were reported in Europe, USA, as well as other parts of the world, giving rise to a pandemic the likes of which haven’t been seen in recent history. The virus, officially called SARS-CoV‑2, spread rapidly, leading to governments imposing a lockdown in most countries. Till date, more than 5.5 million people have been diagnosed with this new disease — COVID-19.
A concerning development that scientists have observed is that the virus is mutating and actively evolving. This gives rise to the question — does this observation have potential implications for the development of a vaccine?
SARS-CoV‑2 is an RNA virus — it stores its genetic information in the form of a molecule called RNA. Just like our DNA, this RNA carries encoded information that allows the virus to survive and replicate. Once the virus infects a cell, this RNA is copied, and the information is used to produce new proteins which are then used to build more viruses. This copying process isn’t perfect and may contain errors. While human cells usually have ‘proofreading’ systems to eliminate such errors, RNA viruses lack these safeguards. As a result, these errors (called ‘mutations’) tend to accumulate in their genome over time. This gradual process in which the mutations slowly become fixed in the genome is known as evolution.
Such errors in the code can lead to the synthesis of altered viral proteins which may behave differently from the original ones. Sufficiently altered genetic codes can give rise to a completely new strain of the virus. Mutations can change a virus’s properties — some can stop the immune system from recognizing it, while others can help it develop drug resistance. This can have an impact on how a viral infection is treated.
When samples from COVID-19 patients are studied, these mutations show up as variations in the genetic code of the virus. While researchers have observed such variations in the novel coronavirus, till date, individual strains of SARS-CoV‑2 haven’t been known to cause different symptoms.
A recent study by Ziljie Shen and colleagues from the Chinese Academy of Sciences, Beijing, uses RNA sequencing to shed light on the diversity of genomic changes in SARS-CoV‑2. RNA is composed of many individual units (called nucleotides) strung together in a chain, whose sequence encodes vital information. RNA sequencing is a technique that allows researchers to read this code. The study involved sequencing the fluid found in the lungs of 8 CoV‑2 patients, 25 common pneumonia patients, and 20 healthy people. The researchers found diverse viral RNA sequences in the patient samples and identified a few specific locations on the virus’s genome where the sequence varied a lot from patient to patient.
Other studies have reported similar findings. In one such study, researchers from the University of Pittsburgh Medical Center, USA, compared 86 genomes to show the diversity in SARS-CoV‑2 strains isolated from different parts of the world.
Large online databases have also been built to store SARS-CoV‑2 genomes and to track mutations as they arise. These include ViPR , COVID-19 UniProtKB, hCov-19. The COVID-19 GenomePedia is a resource created by Vinod Scaria’s lab at the Institute of Genomics and Integrated Biology (IGIB), New Delhi, to collate information on SARS-CoV‑2 genomes sequenced in India as well as other parts of the world.
A quick search of GenomePedia shows that Indian labs have sequenced at least 118 SARS-CoV‑2 genomes so far, with contributions from institutes including but not limited to National Centre for Disease Control (NCDC), Delhi; National Institute of Virology (NIV), Pune; National Institute of Biomedical Genomics (NIBMG), Kalyani; Gujarat Biotechnology Research Centre (GBRC), Gandhinagar; National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru; and Gandhi Medical College, Secunderabad.
As studies on other viruses have shown, in a diverse viral population, some viruses will be able to adapt to the host’s body, and hence survive longer. Such viruses could have modified genetic codes which may allow them to go undetected by immune cells. On a positive note, however, SARS-CoV‑2 appears to mutate more slowly than common and more infectious viruses e.g. flu virus, and viral sequences isolated from different patients are almost identical with greater than 99.9 per cent sequence identity.
In an interview with Healthline, Benjamin Neuman, Head of Biology at Texas A&M University-Texarkana, says that most mutations tend to impair a virus’s functioning and that it is common for mutations is to appear and die out again quickly. Generally, new variants of a virus retain many features of older strains. Therefore, despite the accumulation of mutations, it’s unusual to find viruses that, over short time scales, would change to such an extent that it makes them resistant to a vaccine. This gives hope for the potential development of effective long-lasting vaccines against the virus.